Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug
resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting Pgp
to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp.
Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism
design on the basis of Dimethyl Cardamonin (DMC). Subsequently, we evaluated their reversal activities
as potential P-glycoprotein (P-gp)-mediated Multidrug Resistance (MDR) agents.
Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the corresponding
benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. Their cytotoxicity
and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 was evaluated
by Doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply.
Results and Discussion: The results showed that compounds B2, B4 and B6 had the potency of
MDR reversers with little intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the
capability to inhibit MCF-7 and MCF-7/DOX cells migration. Besides, the most compound B4 was
selected for further study, which promoted the accumulation of DOX in MCF-7/DOX cells and inhibited
the expressionof P-gp at protein levels.
Conclusion: The above findings may provide new insights for the research and development of Pgp-
mediated MDR reversal agents.